Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Institute of Immunology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
United European Gastroenterol J. 2022 Apr;10(3):319-329. doi: 10.1002/ueg2.12218. Epub 2022 Mar 15.
BACKGROUND/AIMS: In this observational study, we explored the humoral and cellular immune response to SARS-CoV-2 vaccination in patients with autoimmune hepatitis (AIH) and patients with cholestatic autoimmune liver disease (primary sclerosing cholangitis [PSC] and primary biliary cholangitis [PBC]).
Anti-SARS-CoV-2 antibody titers were determined using the DiaSorin LIAISON and Roche immunoassays in 103 AIH, 64 PSC, and 61 PBC patients and 95 healthy controls >14 days after the second COVID-19 vaccination. The spike-specific T-cell response was assessed using an activation-induced marker assay (AIM) in a subset of individuals.
Previous SARS-CoV-2 infection was frequently detected in AIH but not in PBC/PSC (10/112 (9%), versus 4/144 (2.7%), p = 0.03). In the remaining patients, seroconversion was measurable in 97% of AIH and 99% of PBC/PSC patients, respectively. However, in 13/94 AIH patients antibody levels were lower than in any healthy control, which contributed to lower antibody levels of the total AIH cohort when compared to PBC/PSC or controls (641 vs. 1020 vs. 1200 BAU/ml, respectively). Notably, antibody levels were comparably low in AIH patients with (n = 85) and without immunosuppression (n = 9). Also, antibody titers significantly declined within 7 months after the second vaccination. In the AIM assay of 20 AIH patients, a spike-specific T-cell response was undetectable in 45% despite a positive serology, while 87% (13/15) of the PBC/PSC demonstrated a spike-specific T-cell response.
Patients with AIH show an increased SARS-CoV-2 infection rate as well as an impaired B- and T-cell response to SARS-CoV-2 vaccine compared to PBC and PSC patients, even in the absence of immunosuppression. Thus, antibody responses to vaccination in AIH patients need to be monitored and early booster immunizations considered in low responders.
背景/目的：在这项观察性研究中，我们探讨了自身免疫性肝炎（AIH）和胆汁淤积性自身免疫性肝病（原发性硬化性胆管炎[PSC]和原发性胆汁性胆管炎[PBC]）患者对 SARS-CoV-2 疫苗接种的体液和细胞免疫反应。
在 103 例 AIH、64 例 PSC 和 61 例 PBC 患者以及 95 例>14 天接受第二次 COVID-19 疫苗接种的健康对照者中，使用 DiaSorin LIAISON 和 Roche 免疫测定法测定抗 SARS-CoV-2 抗体滴度。在一部分个体中，使用激活诱导标记物测定法（AIM）评估刺突特异性 T 细胞反应。
在 AIH 中经常检测到先前的 SARS-CoV-2 感染，但在 PBC/PSC 中未检测到（112 例中的 10 例[9%]，144 例中的 4 例[2.7%]，p=0.03）。在其余患者中，分别有 97%的 AIH 和 99%的 PBC/PSC 患者可检测到血清转换。然而，在 13/94 例 AIH 患者中，抗体水平低于任何健康对照者，这导致与 PBC/PSC 或对照组相比，AIH 总队列的抗体水平较低（分别为 641、1020 和 1200 BAU/ml）。值得注意的是，有（n=85）和无免疫抑制（n=9）的 AIH 患者的抗体水平相当低。此外，在第二次接种后 7 个月内，抗体滴度显著下降。在 20 例 AIH 患者的 AIM 检测中，尽管血清学阳性，但仍有 45%的患者检测不到刺突特异性 T 细胞反应，而 87%（13/15）的 PBC/PSC 患者则表现出刺突特异性 T 细胞反应。
与 PBC 和 PSC 患者相比，AIH 患者的 SARS-CoV-2 感染率增加，对 SARS-CoV-2 疫苗的 B 细胞和 T 细胞反应受损，即使在没有免疫抑制的情况下也是如此。因此，需要监测 AIH 患者对疫苗接种的抗体反应，并考虑对低应答者进行早期加强免疫。
